Gait speed declines at a faster rate in persons with HIV (PWH) than in the general population but the risk factors associated with this decline are not well understood. In the AIDS Clinical Trials Group (ACTG) A5322 (HAILO, HIV Infection, Aging, and Immune Function Long-term Observational Study), an observational cohort study of PWH ≥40 years of age, those who developed slow gait during the first 3 years of follow-up were compared with persons who maintained normal speed. Associations with demographic and clinical covariates were assessed using multivariable logistic regression. Of 929 participants, 81% were men, 31% Black, and 20% Hispanic. Median age was 51 years [interquartile range (IQR) = 46–56]. At study entry, 92% had plasma HIV RNA <50 copies/mL with median CD4 count 631 cells/mm3 (IQR = 458–840). At study entry, 7% of participants had slow gait, 16% had neurocognitive impairment (NCI), and 12% had diabetes. Over 3 years, 87% maintained normal gait speed, 3% maintained a slow gait, 6% developed a slow gait, and 4% improved from slow to normal gait speed. In multivariable models, hemoglobin A1C (HbA1C) percentage, per one unit increase [odds ratio (OR) = 1.36; 95% confidence interval (CI) = 1.03–1.81; p = .033], NCI (OR = 3.47; 95% CI = 1.57–7.69 p = .002), and black versus white race (OR = 2.45; 95% CI = 1.08–5.59; p = .032) at entry were significantly associated with development of slow gait compared with those maintaining normal gait speed. The association between baseline HbA1C and development of slow gait speed highlights an intervenable target to prevent progression of physical function limitations.
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References
1.
DeeksSG: HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med, 2011; 62:141–155.
2.
HasseB, LedergerberB, FurrerH, et al.: Morbidity and aging in HIV-infected persons: The Swiss HIV cohort study. Clin Infect Dis, 2011; 53:1130–1139.
3.
SmitM, BrinkmanK, GeerlingsS, et al.: Future challenges for clinical care of an ageing population infected with HIV: A modelling study. Lancet Infect Dis, 2015; 15:810–818.
4.
DesquilbetL, JacobsonLP, FriedLP, et al.: HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci, 2007; 62:1279–1286.
SchrackJA, JacobsonLP, AlthoffKN, et al.: Effect of HIV-infection and cumulative viral load on age-related decline in grip strength. AIDS, 2016; 30:2645–2652.
7.
JohsNA, WuK, TassiopoulosK, et al.: Disability among middle-aged and older persons with human immunodeficiency virus infection. Clin Infect Dis, 2017; 65:83–91.
8.
SharmaA, HooverDR, ShiQ, et al.: Longitudinal study of falls among HIV-infected and uninfected women: The role of cognition. Antivir Ther, 2018; 23:179–190.
9.
TassiopoulosK, AbdoM, WuK, et al.: Frailty is strongly associated with increased risk of recurrent falls among older HIV-infected adults. AIDS, 2017; 31:2287–2294.
10.
ErlandsonKM, AllshouseAA, JankowskiCM, MawhinneyS, KohrtWM, CampbellTB: Relationship of physical function and quality of life among persons aging with HIV infection. AIDS, 2014; 28:1939–1943.
CesariM, KritchevskySB, PenninxBW, et al.: Prognostic value of usual gait speed in well-functioning older people—Results from the Health, Aging and Body Composition Study. J Am Geriatr Soc, 2005; 53:1675–1680.
13.
GuralnikJM, FerrucciL, PieperCF, et al.: Lower extremity function and subsequent disability: Consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci, 2000; 55:M221–M231.
14.
StudenskiS, PereraS, PatelK, et al.: Gait speed and survival in older adults. JAMA, 2011; 305:50–58.
15.
ErlandsonKM, PerezJ, AbdoM, et al.: Frailty, neurocognitive impairment, or both in predicting poor health outcomes among adults living with human immunodeficiency virus. Clin Infect Dis, 2019; 68:131–138.
16.
FerrucciL, BandinelliS, BenvenutiE, et al.: Subsystems contributing to the decline in ability to walk: Bridging the gap between epidemiology and geriatric practice in the InCHIANTI study. J Am Geriatr Soc, 2000; 48:1618–1625.
17.
SchrackJA, SimonsickEM, ChavesPH, FerrucciL: The role of energetic cost in the age-related slowing of gait speed. J Am Geriatr Soc, 2012; 60:1811–1816.
18.
SchrackJA, ZipunnikovV, SimonsickEM, StudenskiS, FerrucciL: Rising energetic cost of walking predicts gait speed decline with aging. J Gerontol A Biol Sci Med Sci, 2016; 71:947–953.
19.
GuralnikJM, FerrucciL, SimonsickEM, SaliveME, WallaceRB: Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med, 1995; 332:556–561.
20.
ErlandsonKM, NgDK, JacobsonLP, et al.: Inflammation, immune activation, immunosenescence, and hormonal biomarkers in the frailty-related phenotype of men with or at risk for HIV infection. J Infect Dis, 2017; 215:228–237.
21.
SunJ, BrownTT, SamuelsDC, et al.: The role of mitochondrial DNA variation in age-related decline in gait speed among older men living with human immunodeficiency virus. Clin Infect Dis, 2018; 67:778–784.
22.
ErlandsonKM, SchrackJA, JankowskiCM, BrownTT, CampbellTB: Functional impairment, disability, and frailty in adults aging with HIV-infection. Curr HIV/AIDS Rep, 2014; 11:279–290.
23.
TranT, GuardigniV, PencinaKM, et al.: Atypical skeletal muscle profiles in human immunodeficiency virus-infected asymptomatic middle-aged adults. Clin Infect Dis, 2018; 66:1918–1927.
24.
BernerK, MorrisL, BaumeisterJ, LouwQ: Objective impairments of gait and balance in adults living with HIV-1 infection: A systematic review and meta-analysis of observational studies. BMC Musculoskelet Disord, 2017; 18:325.
25.
ErlandsonKM, WuK, KoletarSL, et al.: Association between frailty and components of the frailty phenotype with modifiable risk factors and antiretroviral therapy. J Infect Dis, 2017; 215:933–937.
26.
BauerLO, WuZ, WolfsonLI: An obese body mass increases the adverse effects of HIV/AIDS on balance and gait. Phys Ther, 2011; 91:1063–1071.
27.
McInerneyPA, NcamaBP, WantlandD, et al.: Quality of life and physical functioning in HIV-infected individuals receiving antiretroviral therapy in KwaZulu-Natal, South Africa. Nurs Health Sci, 2008; 10:266–272.
28.
RichertL, BraultM, MercieP, et al.: Decline in locomotor functions over time in HIV-infected patients. AIDS, 2014; 28:1441–1449.
29.
SafeekRH, HallKS, LobeloF, et al.: Low levels of physical activity among older persons living with HIV/AIDS are associated with poor physical function. AIDS Res Hum Retroviruses, 2018; 34:929–935.
30.
RobertsonKR, ParsonsTD, SidtisJJ, et al.: Timed Gait test: Normative data for the assessment of the AIDS dementia complex. J Clin Exp Neuropsychol, 2006; 28:1053–1064.
31.
FriedLP, TangenCM, WalstonJ, et al.: Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci, 2001; 56:M146–M156.
32.
KleinS, AllisonDB, HeymsfieldSB, et al.: Waist circumference and cardiometabolic risk: A consensus statement from shaping America's health: Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Diabetes Care, 2007; 30:1647–1652.
33.
RobertsonKR, SmurzynskiM, ParsonsTD, et al.: The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS, 2007; 21:1915–1921.
34.
EllisRJ, EvansSR, CliffordDB, et al.: Clinical validation of the NeuroScreen. J Neurovirol, 2005; 11:503–511.
35.
AtkinsonHH, RosanoC, SimonsickEM, et al.: Cognitive function, gait speed decline, and comorbidities: The health, aging and body composition study. J Gerontol A Biol Sci Med Sci, 2007; 62:844–850.
36.
RossoAL, VergheseJ, MettiAL, et al.: Slowing gait and risk for cognitive impairment: The hippocampus as a shared neural substrate. Neurology, 2017; 89:336–342.
37.
KallianpurKJ, SakodaM, GangcuangcoLM, et al.: Frailty characteristics in chronic HIV patients are markers of white matter atrophy independently of age and depressive symptoms: A Pilot Study. Open Med J, 2016; 3:138–152.
38.
De RekeneireN, ResnickHE, SchwartzAV, et al.: Diabetes is associated with subclinical functional limitation in nondisabled older individuals: The Health, Aging, and Body Composition study. Diabetes Care, 2003; 26:3257–3263.
39.
GreggEW, BecklesGL, WilliamsonDF, et al.: Diabetes and physical disability among older U.S. adults. Diabetes Care, 2000; 23:1272–1277.
40.
KalyaniRR, TraY, YehHC, EganJM, FerrucciL, BrancatiFL: Quadriceps strength, quadriceps power, and gait speed in olderU.S. adults with diabetes mellitus: Results from the National Health and Nutrition Examination Survey, 1999–2002. J Am Geriatr Soc, 2013; 61:769–775.
41.
KuoCK, LinLY, YuYH, WuKH, KuoHK: Inverse association between insulin resistance and gait speed in nondiabetic older men: Results from theU.S. National Health and Nutrition Examination Survey (NHANES) 1999–2002. BMC Geriatr, 2009; 9:49.
42.
OkoroCA, ZhongY, FordES, BalluzLS, StrineTW, MokdadAH: Association between the metabolic syndrome and its components and gait speed amongU.S. adults aged 50 years and older: A cross-sectional analysis. BMC Public Health, 2006; 6:282.
43.
ParkSW, GoodpasterBH, StrotmeyerES, et al.: Decreased muscle strength and quality in older adults with type 2 diabetes: The health, aging, and body composition study. Diabetes, 2006; 55:1813–1818.
44.
PhielixE, MensinkM: Type 2 diabetes mellitus and skeletal muscle metabolic function. Physiol Behav, 2008; 94:252–258.
45.
FigaroMK, KritchevskySB, ResnickHE, et al.: Diabetes, inflammation, and functional decline in older adults: Findings from the Health, Aging and Body Composition (ABC) study. Diabetes Care, 2006; 29:2039–2045.
46.
UmegakiH, MakinoT, UemuraK, et al.: The Associations among insulin resistance, hyperglycemia, physical performance, diabetes mellitus, and cognitive function in relatively healthy older adults with subtle cognitive dysfunction. Front Aging Neurosci, 2017; 9:72.
47.
YangJ, JacobsonLP, BeckerJT, et al.: Impact of glycemic status on longitudinal cognitive performance in men with and without HIV infection. AIDS, 2018; 32:1849–1860.
48.
KhuderSS, ChenS, LetendreS, et al.: Impaired insulin sensitivity is associated with worsening cognition in HIV-infected patients. Neurology, 2019; 92:e1344–e1353.
49.
WuM, FatukasiO, YangS, et al.: HIV disease and diabetes interact to affect brain white matter hyperintensities and cognition. AIDS, 2018; 32:1803–1810.
50.
SuT, WitFW, CaanMW, et al.: White matter hyperintensities in relation to cognition in HIV-infected men with sustained suppressed viral load on combination antiretroviral therapy. AIDS, 2016; 30:2329–2339.
51.
LevettTJ, CresswellFV, MalikMA, FisherM, WrightJ: Systematic review of prevalence and predictors of frailty in individuals with human immunodeficiency virus. J Am Geriatr Soc, 2016; 64:1006–1014.
52.
AroAK, KarjalainenM, TiihonenM, et al.: Glycemic control and health-related quality of life among older home-dwelling primary care patients with diabetes. Prim Care Diabetes, 2017; 11:577–582.
53.
RizzoMR, BarbieriM, FavaI, et al.: Sarcopenia in elderly diabetic patients: Role of dipeptidyl peptidase 4 inhibitors. J Am Med Dir Assoc, 2016; 17:896–901.
54.
LaksmiPW, SetiatiS, TaminTZ, et al.: Effect of metformin on handgrip strength, gait speed, myostatin serum level, and health-related quality of life: A double blind randomized controlled trial among non-diabetic pre-frail elderly patients. Acta Med Indones, 2017; 49:118–127.
55.
GuaraldiG, MalagoliA, CalcagnoA, et al.: The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: A cross sectional study of people aged 65–74 years and more than 75 years. BMC Geriatr, 2018; 18:99.
56.
American Geriatrics Society Expert Panel on Care of Older Adults with Diabetes M, MorenoG, MangioneCM, KimbroL, VaisbergE: Guidelines abstracted from the American Geriatrics Society Guidelines for Improving the Care of Older Adults with Diabetes Mellitus: 2013 update. J Am Geriatr Soc, 2013; 61:2020–2026.
57.
KimTW, WalleyAY, VenturaAS, et al.: Polypharmacy and risk of falls and fractures for patients with HIV infection and substance dependence. AIDS Care, 2018; 30:150–159.
58.
YarasheskiKE, CadeWT, OvertonET, et al.: Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. Am J Physiol Endocrinol Metab, 2011; 300:E243–E251.
59.
FitchKV, AndersonEJ, HubbardJL, et al.: Effects of a lifestyle modification program in HIV-infected patients with the metabolic syndrome. AIDS, 2006; 20:1843–1850.
60.
DuncanAD, GoffLM, PetersBS: Type 2 diabetes prevalence and its risk factors in HIV: A cross-sectional study. PLoS One, 2018; 13:e0194199.
61.
ByrneH, CaulfieldB, De VitoG: Effects of self-directed exercise programmes on individuals with type 2 diabetes mellitus: A systematic review evaluating their effect on HbA1c and other metabolic outcomes, physical characteristics, cardiorespiratory fitness and functional outcomes. Sports Med, 2017; 47:717–733.
62.
AlletL, ArmandS, de BieRA, et al.: The gait and balance of patients with diabetes can be improved: A randomised controlled trial. Diabetologia, 2010; 53:458–466.
63.
MontoyaJL, JankowskiCM, O'BrienKK, et al.: Evidence-informed practical recommendations for increasing physical activity among persons living with HIV. AIDS, 2019; 33:931–939.
64.
KosterA, PenninxBW, BosmaH, et al.: Is there a biomedical explanation for socioeconomic differences in incident mobility limitation?. J Gerontol A Biol Sci Med Sci, 2005; 60:1022–1027.
65.
ThorpeRJJr., KosterA, KritchevskySB, et al.: Race, socioeconomic resources, and late-life mobility and decline: Findings from the Health, Aging, and Body Composition study. J Gerontol A Biol Sci Med Sci, 2011; 66:1114–1123.
66.
LouieGH, WardMM: Socioeconomic and ethnic differences in disease burden and disparities in physical function in older adults. Am J Public Health, 2011; 101:1322–1329.
67.
LeveilleSG, ThapaS: Disability among persons aging with HIV/AIDS. Interdiscip Top Gerontol Geriatr, 2017; 42:101–118.
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